# Regulation of Ubiquitination and Arthritis

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $403,750

## Abstract

Project Summary/Abstract
Arthritides are chronic, progressive systemic inflammatory diseases that lead to significant joint damage, pain,
dysfunction, and disability. A20, also known as TNFAIP3, is genetically and epigenetically linked to human
arthritis, and recent experimental studies implicate A20 in regulating several potential pathophysiological
arthritis pathways. Mice bearing A20 deficient dendritic cells or A20 deficient macrophages/neutrophils
spontaneously develop arthritis. A20 restricts several inflammatory pathways, including TLR, TNFα, and
inflammasome signals. How A20 performs these critical functions and prevents arthritis are poorly understood.
A20 has multiple motifs that mediate deubiquitinating, ubiquitin binding, and E3 ubiqutin ligase activities. The
goal of this proposal is to understand the biochemical mechanisms by which A20 prevents arthritis. We have
generated several knock-in lines of mice with strategic point mutations that abrogate specific biochemical
functions of A20. Using these new mouse strains, we will determine which of A20's ubiquitin dependent
functions preserve the cellular and molecular pathways that prevent arthritis. The proposed studies will
establish a new robust mouse model of spontaneous arthritis based on a human arthritis susceptibility protein.

## Key facts

- **NIH application ID:** 10150740
- **Project number:** 5R01AI135198-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** AVERIL I MA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $403,750
- **Award type:** 5
- **Project period:** 2018-05-05 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10150740

## Citation

> US National Institutes of Health, RePORTER application 10150740, Regulation of Ubiquitination and Arthritis (5R01AI135198-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10150740. Licensed CC0.

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